rs145210051

chr14-91279299-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_001080414.4(CCDC88C):c.4707G>A(p.Arg1569=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,599,192 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (13 hom.)
• Consequence: CCDC88C NM_001080414.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.668

Genes affected

CCDC88C (HGNC:19967): (coiled-coil domain containing 88C) This gene encodes a ubiquitously expressed coiled-coil domain-containing protein that interacts with the dishevelled protein and is a negative regulator of the Wnt signalling pathway. The protein encoded by this gene has a PDZ-domain binding motif in its C-terminus with which it interacts with the dishevelled protein. Dishevelled is a scaffold protein involved in the regulation of the Wnt signaling pathway. The Wnt signaling pathway plays an important role in embryonic development, tissue maintenance, and cancer progression. Mutations in this gene cause autosomal recessive, primary non-syndromic congenital hydrocephalus; a condition characterized by excessive accumulation of cerebrospinal fluid in the ventricles of the brain. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 14-91279299-C-T is Benign according to our data. Variant chr14-91279299-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 447021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91279299-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.668 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00326 (4724/1446914) while in subpopulation MID AF= 0.00887 (51/5750). AF 95% confidence interval is 0.00693. There are 13 homozygotes in gnomad4_exome. There are 2253 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88C	NM_001080414.4	c.4707G>A	p.Arg1569=	synonymous_variant	28/30	ENST00000389857.11
CCDC88C	XM_011536796.3	c.4599G>A	p.Arg1533=	synonymous_variant	28/30
CCDC88C	XM_047431418.1	c.4440G>A	p.Arg1480=	synonymous_variant	25/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88C	ENST00000389857.11	c.4707G>A	p.Arg1569=	synonymous_variant	28/30	5	NM_001080414.4	P1
CCDC88C	ENST00000334448.5	n.519G>A		non_coding_transcript_exon_variant	4/6	1
CCDC88C	ENST00000556726.5	c.*541G>A		3_prime_UTR_variant	5/7	5
CCDC88C	ENST00000557455.1	n.679G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 342 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00269 AC: 608 AN: 225902 Hom.: 1 AF XY: 0.00251 AC XY: 306 AN XY: 121890

Gnomad AFR exome AF: 0.000736

Gnomad AMR exome AF: 0.00337

Gnomad ASJ exome AF: 0.00541

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000363

Gnomad FIN exome AF: 0.000441

Gnomad NFE exome AF: 0.00385

Gnomad OTH exome AF: 0.00584

GnomAD4 exome AF: 0.00326 AC: 4724 AN: 1446914 Hom.: 13 Cov.: 30 AF XY: 0.00314 AC XY: 2253 AN XY: 718286

Gnomad4 AFR exome AF: 0.000720

Gnomad4 AMR exome AF: 0.00364

Gnomad4 ASJ exome AF: 0.00525

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000418

Gnomad4 FIN exome AF: 0.000323

Gnomad4 NFE exome AF: 0.00372

Gnomad4 OTH exome AF: 0.00339

GnomAD4 genome AF: 0.00225 AC: 342 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.00197 AC XY: 147 AN XY: 74464

Gnomad4 AFR AF: 0.000891

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00348

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00332 Hom.: 1

Bravo AF: 0.00245

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	CCDC88C: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	7.1
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145210051; hg19: chr14-91745643; COSMIC: COSV100484914;